This application for a SCOR in Congenital Heart Disease is to initiate and coordinate research related to the development of congenital cardiac defects. The program consists of five projects which will carry out studies of 1) the genetic epidemiology of endocardial cushion defects occurring in children; 2) the earliest formation of precardiac cells and supporting matrix in mammalian embryos; 3) the molecular interactions which lead to epithelial-mesenchymal transformation which in turn lead to the completion of the atrioventricular canal during embryogenesis; 4) the molecular genetic control of biochemistry resulting in the changes of myofibrillar proteins in embryonic through mature mammalian development; and 5) the ontogenesis of hypertrophic cardiomyopathy prior to the development of the interventricular septum through the immediate post natal period in the rat model. These studies will be coordinated by an Administrative Core and will utilize a Biostatistical Core for experimental design, data management an data analyses. In addition, a Molecular Biology Core Laboratory will permit bulk purchase of unique reagents and biologicals, will facilitate the development of new technologies and will carry out human DNA studies. The program involves scientists with appointments in Anatomy, Biochemistry, Biology, Pediatrics (Cardiology and Genetics), and Preventive Medicine (Biostatistics). The research is sponsored by the University of Iowa Cardiovascular Research Center, which provides a continuing forum for research review, consultation and integration.